https://scholar.dgist.ac.kr/handle/20.500.11750/287 2026-04-24T18:31:17Z https://scholar.dgist.ac.kr/handle/20.500.11750/60202 Title: Cereblon (CRBN) inhibits prostate cancer metastasis by negatively regulating 6-phosphogluconate dehydrogenase (6PGD) Author(s): Guchhait, Koushik; Yoon, Hyeon-Seung; An, Hyun-Su; Shin, Seungheon; Nam, Hye Seung; Yanqui-Rivera, Francisco D.; Ona, Samara M.; Mendez, Miguel A.; Hwang, Jong Yeon; Park, Daeho; Park, Chul-Seung; Han, Jee-Young; Chung, Doo Yong; Park, Seokjae; Kim, Eun-Kyoung; Yang, Su-Geun; Cho, Steve K. Abstract: Metastasis is the primary cause of mortality in advanced prostate cancer, and the emergence of resistance to androgen receptor (AR)-targeted therapies highlights the urgent need for alternative therapeutic strategies. Metabolic reprogramming has increasingly been recognized as a key driver of metastatic progression. In this study, we uncover a novel tumor-suppressive role for cereblon (CRBN), a substrate receptor of the CRL4CRBN E3 ubiquitin ligase complex, in modulating prostate cancer metastasis through regulation of 6-phosphogluconate dehydrogenase (6PGD), a critical enzyme in the oxidative pentose phosphate pathway (oxPPP). CRBN directly binds a conserved C-terminal alpha-helix in 6PGD, promoting its polyubiquitination and proteasomal degradation independently of immunomodulatory drugs (IMiDs). Genetic or pharmacological loss of CRBN via CRISPR/Cas9, RNA interference, or PROTAC-mediated degradation stabilized 6PGD and elevated the NADPH/NADP+ ratio. Conversely, re-expression of wild-type CRBN reduced 6PGD levels, restored NADPH/NADP+ ratio, and suppressed cell migration and invasion. Transcriptomic profiling revealed CRBN-induced upregulation of CDH1 and downregulation of the EMT marker MMP1, while CRBN degradation produced the opposite pattern-both effects were reversed by 6PGD inhibition. These regulatory effects were conserved across multiple cancer cell lines and observed in CRBN-deficient mouse tissues. Functional studies using intra-splenic xenograft models further demonstrated that CRBN suppresses metastatic dissemination. Collectively, our findings identify 6PGD as a novel endogenous substrate of CRBN and establish the CRBN-6PGD axis as a critical metabolic checkpoint in prostate cancer metastasis. Therapeutic targeting of this pathway may offer promising strategies for CRBN-deficient or 6PGD-driven cancers. 2026-02-28T15:00:00Z https://scholar.dgist.ac.kr/handle/20.500.11750/59920 Title: Threonic acid, an ascorbic acid metabolite, synergizes with intermittent fasting to ameliorate obesity Author(s): Oh, Sungjoon; Park, Seokjae; Kim, Eun-Kyoung Abstract: Intermittent fasting (IF) is a safe and sustainable approach for obesity treatment, yet its weight loss efficacy is relatively modest compared with that of pharmacologic anti-obesity therapies. The synergistic benefits of pairing IF with administration of nutrient-derived metabolites remain poorly understood. Here we report that combining IF with threonic acid (TA), an ascorbic acid metabolite, led to more pronounced reductions in body weight and food intake, as well as improvements in energy expenditure and glycemic control, compared with either intervention alone in diet-induced obese mice. These metabolic benefits were associated with the anorexigenic role of TA in reversing fasting-induced upregulation of the hypothalamic orexigenic neuropeptides NPY and AGRP. In the hypothalamus, TA competed with glucose for uptake via glucose transporter 3 (GLUT3), while IF boosted the TA uptake through both glucose depletion and upregulation of GLUT3, resulting in a more robust suppression of NPY and AGRP expression. Collectively, our findings highlight the combination of TA with IF as a promising metabolite-based combinatorial strategy to enhance the therapeutic efficacy of obesity treatment. 2025-12-31T15:00:00Z https://scholar.dgist.ac.kr/handle/20.500.11750/59011 Title: Metabolomic profiling in blood of pancreatic cancer patients Author(s): Kim, Hyojeong; Kim, Dong-uk; Choe, Sangmin; Lee, SeungHun; Kim, Eun-Kyoung; Park, Seokjae Abstract: Background Pancreatic cancer has a poor prognosis. One of the reasons is that it is difficult to diagnose early. There has been abundant evidence that malignant cells rewire their metabolism to survive and proliferate. This study examined differentia of metabolomic profiling between patients with advanced pancreatic cancers and volunteers without ones. Methods Ten patients and 10 volunteers who aged 20 years or older were enrolled between May and December 2015. The patients had been confirmed as pancreatic ductal adenocarcinoma cytologically or histologically. The volunteers were those who had examined abdomen CT during their health screenings and had no evidence suggesting pancreatic cancer. Blood plasma samples were derivatized and analyzed by gas chromatography mass spectrometry (GC-MS). GC-MS (Agilent 5975C MSD + 7890A GC) data produced by untargeted method were analyzed by statistical methods including principal Component Analyses (PCA). Results Lactic acid showed significantly high concentration with fold change of 3.23 in patients group (P ≤ 0.0001). 1,5-Anhydroglucitol was decreased with fold change of 2.94 in patients group (P ≤ 0.0001). Conclusion This study suggest that pancreatic cancer patients could have different metabolomic profiling from normal population. Further investigation is required for the development of early diagnosis as well exploration of potentially therapeutic target. 2017-07-26T15:00:00Z https://scholar.dgist.ac.kr/handle/20.500.11750/58792 Title: PHARMACEUTICAL COMPOSITION FOR PREVENTING OR TREATING OBESITY CONTAINING BIGLYCAN AS ACTIVE INGREDIENT Author(s): 김은경; 김설송; 김현수 Abstract: The present invention relates to a pharmaceutical composition which is for preventing or treating obesity, and contains biglycan as an active ingredient. Biglycan according to the present invention induces appetite suppression by suppressing the expression of Agrp and NPY, which are appetite promoting peptides, and increasing the expression of POMC, which is an appetite suppressing peptide, and thus is very useful as a medicine for treating obesity.